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Each episode features The Cat in the Hat (voiced by Martin Short),[1] who leads six-year-old neighbours Nick and Sally, the Fish, and Thing One and Thing Two on a variety of adventures in his "Thinga-ma-jigger", a Seussian contraption that can sprout wings, pontoons, booster rockets, change size, and do just about anything else necessary to further the adventure. The adventures are prompted by a question posed by either Nick or Sally at the beginning of each episode,[3] which will inevitably lead them around the globe to "make natural science discoveries."[4] Similar to other PBS Kids series such as Curious George and Sid the Science Kid, The Cat in the Hat Knows a Lot About That! focuses on introducing preschoolers to various science and learning concepts.

The Cat in the Hat – Voiced by Martin Short and Keith Wickham in the U.K. A knowledgeable, adventurous, anthropomorphic cat. He loves to explore the world and act as Nick and Sally's guide, and he frequently speaks in rhyming patterns reminiscent of the Dr. Seuss character on which he is based.

Nick – Voiced by Jacob Ewaniuk and Bob Lloyd in the U.K. A seven-year-old boy. He is Sally's next door neighbour and best friend. He wears an orange sweater, white short-sleeves-undershirt, blue pants, and gray shoes with black soles.

Sally – Voiced by Alexa Torrington and Joanna Ruiz in the U.K. A six-year-old girl. She is Nick's next door neighbour and best friend. She wears a dark pink headband, short-sleeved white undershirt, a dark pink jumper with 2 matching buttons, and dark pink Mary-Jane shoes with brown soles.

Fish – Voiced by Rob Tinkler and Simon Greenall in the U.K. A moderately pessimistic fish who is loosely based on the fish in the original story. Unlike the fish in the book, however, he is red and appears to belong to the Cat instead of Sally or Nick. He is also much more cooperative in the Cat's adventures.

Thing One and Thing Two – Also voiced by Rob Tinkler. The Cat's two zany, energetic helpers of indeterminate species.

Sally's mom – Voiced by Tracey Hoyt. Whenever Sally asks permission to go on an adventure with the Cat, her voice is heard responding. In some of the episodes, she appears.

Nick's mom – Also voiced by Tracey Hoyt. Whenever Nick asks permission to go on an adventure with the Cat, her voice is heard responding. In some of the episodes, she appears. She talks with a Jamaican accent.

Zhu Zhu – Voiced by Heather Bambrick. Zhu Zhu is a giant panda enlisted by the Cat, Sally, and Nick to find a present for their panda. She appears in "Bamboozled" where she lives in the forest of Bamwamabooboo.

Various DVDs were released by NCircle Entertainment beginning in late October 2010 where every DVD is in region 1, subtitled in English and Spanish, approximately 60 minutes except for a few, in Dolby Digital, in 5.1 surround and Dolby surround stereo in Spanish. Every DVD has the bonus segments from the show.